P2X3受体在糖尿病神经病理性疼痛模型中的作用

The role of P2X3 receptor in diabetic neuropathic pain model

目的观察P2X3受体在糖尿病神经病理性疼痛大鼠模型中的作用和意义。方法将40只SD大鼠随机分为造模组(n=30)和对照组(n=10)。按照60 mg/kg一次性腹腔注射链脲佐菌素(STZ)建立糖尿病大鼠模型。于STZ注射前和注射后第7、14、28天分别测定大鼠血糖、体重以及机械性痛阈的变化。造模组又均分为造模1周组、造模2周组、造模4周组三个亚组。在造模前及造模后1、2、4周利用von Frey hairs法测定大鼠机械痛阈,并通过Real-time法测定每个时间点大鼠脊髓背根神经节(DRG)P2X3受体的表达水平。结果肉眼观察糖尿病大鼠毛色暗淡,尾静脉采血点愈合缓慢,每日饮水,饮食,尿量显著增加,表现符合糖尿病大鼠的临床特征。各模型组血糖浓度均>16.7 mmol/L,各模型组与对照组比较,差异有统计学意义(P<0.01)。糖尿病大鼠体重较对照组同期大鼠增长缓慢,差异有统计学意义(P<0.01)。造模组机械痛阈在造模1周后明显下降(P<0.01),并持续至4周(P<0.01);在造模1周后脊髓DRG内P2X3受体表达水平出现显著上调(P<0.01)。大鼠P2X3受体表达水平变化与机械痛阈的下降存在相关性。结论糖尿病早期大鼠脊髓DRG P2X3受体表达即出现上调,并与疼痛相关,说明P2X3受体可能在糖尿病大鼠周围神经疼痛的发生及痛敏的维持阶段起重要作用。

Objective To investigate the role and significance of P2X3 receptor in the rat model with diabetic neuropathic pain. Methods SD rats（n=40） were randomly divided into the model group（n=30） and control group（n=10）.The rat model with diabetic was induced by intraperitoneal injection of a single dose of streptozotocin（STZ）（60 mg/kg body weight）.Rat blood glucose,weight and mechanical pain threshold changes was detected before injection of STZ and after injecting on day 7,14,28.The model group was consisted modeling one week group,molding two weeks group and molding 4 weeks group.The methods of von Frey hairs and Real-time PCR were adopted to measure respectively the mechanical pain threshold in rats and the expression of P2X3 receptor in dorsal root ganglion（DGR） before modeling and after modeling at 1,2,4 weeks. Results The characteristic of dim coat,slow healing blood point in tail vein and significant increase of drinking water,diet and urine output in diabetic rats was showed,which was correspond with the clinical features of diabetic rats.Blood glucose concentrations was higher than 16.7 mmol/L in each model group and the difference between model group and control group was significant（P〈0.01）.Moreover,the weight in diabetic rats growed slowly compared with the normal rats which had significant difference（P〈0.01）.The mechanical pain threshold of diabetic group was decreased after modeling one week and continued until four weeks（P〈0.01）,while the level of P2X3 receptor was uncommonly up-regulated after molding one week（P〈0.01）.And the changes of P2X3 receptor expression was correlated with the decline of mechanical pain threshold.Conclusion The expression of P2X3 receptor in DRG of early diabetic rat is increased and associated with pain.These results indicate that P2X3 receptor may play an important role in the peripheral nerve pain and hyperalgesia maintenance phase of diabetic rat.